Related research is focusing on developing a strain of mice in which expression of the D2 receptor can be turned up or down, much like adjusting the volume control on a radio. In the drinking study, mice with half the D2 gene appeared to have normal drinking behavior, but their locomotor activity was altered. "There are probabaly many different combinations of effects between full function of this gene and a missing gene," said Malcolm Low, M.D., Ph.D., staff scientist at OHSU's Vollum Institute for Advanced Biomedical Research, associate professor of biochemistry and molecular biology and senior author on the article. Low is a neuroendocrinologist whose laboratory has produced many new strains of mice carrying specific gene mutations. Low's lab is now working on generating mice in which D2 expression can be regulated. "D2 is expressed in many parts of the brain. In some areas the receptor is important for locomotion, in others D2 receptors regulate the synthesis and release ! ! of dopamine itself. Continuing work will focus on isolating the location of the D2 receptors and zeroing in on the role they play in alcoholism," said Low.

While this research was done on mice, Phillips says it could have implications for treating alcoholism in humans. "Suppose you could create a drug that bound to the D2 receptor so that dopamine couldn't bind to that receptor at all. That would be like getting rid of the receptor. If you could do that, then you might be able to reduce drinking. However, the key will be battling the possible adverse side effects of such a drug, since dopamine is critically involved in many normal nervous system functions."

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Contact: Henry Sessions
sessionh@ohsu.edu
503-494-8231
Oregon Health & Science University
20-Oct-1998

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